Synthesis, biological evaluation, molecular docking and MD simulation studies of some new picolinohydrazide derivatives as cholinesterase inhibitors

Kuştan F., Sıcak Y., Mali S. N., Chaudhari S. Y., Öztürk M., TOK F.

Journal of Molecular Structure, cilt.1349, 2026 (SCI-Expanded, Scopus) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1349
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.molstruc.2025.143637
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: AChE, BChE, Antioxidant, MD simulation, Hydrazone, Picolinohydrazide
  • Marmara Üniversitesi Adresli: Evet

Özet

Cholinesterase inhibitors play an important role in the fight against Alzheimer's disease. For this purpose, some new N'-substitutedbenzylidene-6-methylpicolinohydrazide derivatives (3a-3k) were synthesized sequentially under hydrazide and hydrazone reaction conditions, beginning with the starting material ethyl 6-methylpicolinate. Their structures were elucidated by some spectral techniques (IR, 1H-NMR, 13C-NMR, 13C-APT NMR, 2D-NMR). In vitro antioxidant (ABTS˙+, DPPH˙, CUPRAC and β-carotene/linoleic acid assays) and cholinesterase (AChE and BChE) inhibitory activities of the synthesized compounds were tested. Compound 3f, which carries a nitro group on the phenyl ring in the series, was found to have the highest antioxidant activity. The same derivative (3f) was observed to have the highest inhibition values against both AChE and BChE with IC50 values of 0.99±0.04 µM and 10.16±0.27 µM, respectively. The interactions of the most potent compound 3f with AChE and BChE enzymes were explained by molecular docking and MD simulation studies. All compounds were found to be compatible with drug-like properties and non-toxic by in silico methods.